Nebulizer vial for aerosol therapy

ABSTRACT

The nebulizer vial for aerosol therapy comprising a tube fed at a first end with compressed air, the tube being constricted at its second end prior to the relative exit orifice to obtain a venturi effect. The orifice of the tube emerges from the free surface of a solution of an aerosol therapy medicament, a nozzle being concentrically mounted on the second end of the tube such that between the tube and nozzle there remains an interspace communicating with the solution. A flow breaker device is provided above the orifice of the nozzle. The vial is provided with an exit for the formed aerosol and an inlet for entry of external air as a result of suction exerted by the patient on the exit. For diameter parity of the orifice of the nozzle, elements are provided to vary the distance between the nozzle orifice and the flow breaker device.

CROSS REFERENCE TO RELATED APPLICATION

This is the 35 USC 371 national stage of International ApplicationPCT/EP01/09105 filed on Aug. 7, 2001, which designated the United Statesof America.

BACKGROUND OF THE INVENTION

Known nebulizer vials for aerosol therapy are of plastic constructionand use the venturi principle, in particular the so-called doubleventuri, in the sense that the air originating from a compressor ispassed at high velocity through a small-diameter tube constrictedinternally (to form the venturi) and terminating with an orifice whichemerges from the free surface of a solution of an aerosol therapymedicament contained in a reservoir. A nozzle is mounted concentricallyon the end of said tube such that between the nozzle and the tube, thereis an interspace communicating lowerly with the solution contained inthe reservoir. The compressed air leaving the orifice of said tubecauses the particles or droplets of the medicament solution to be suckedupwards through said interspace, to form an upwardly directed stream ofsolution particles, which leaves the nozzle orifice. The stream ofsolution particles formed in this manner is atomized (to form theaerosol) by causing the stream to strike against a flow breaker devicepositioned above the nozzle orifice. The flow breaker device ispositioned at, but without completely closing, the lower end of aconduit through which external air can enter the vial followinginhalation by the patient on an aerosol exit conduit with which the vialis provided.

As known to the expert of this sector, the characteristic parameters ofa therapeutic aerosol are the mass median aerodynamic diameter(indicated by the initials MMAD which depends on the orifice diameter ofthe nozzle), the geometric standard deviation (indicated by the initialsGSD) and the nebulization rate.

The MMAD provides an indication of the average dimensions of theparticles forming the aerosol, this identifying the region of the airpassageways in which the nebulized medicament will deposit.

The GSD enables the degree of dispersion of the solution particledimensions within the distribution to be evaluated.

Finally, the nebulization rate is essentially an index of the mass ofmedicament nebulized per unit of time.

The MMAD and the GSD can both be obtained from the aerosol particlediameter distribution: the MMAD is in fact the aerodynamic diameter towhich 50% of the aerosol particle diameter distribution corresponds; theGSD can be calculated from the particle diameter distribution graph, ifthe distribution is sufficiently linear between 10% and 90%, i.e. if thedistribution is Gaussian, by using suitable extrapolation calculationmethods (see ISO 9276-2).

The medical literature has established that, for therapeutic purposes,those regions of a patient's respiratory tract reachable by the aerosolare related to the dimensions of the medical solution particles inhaled.More precisely, aerodynamic particle diameters greater than 5 micronsare adequate for treatment of the upper air passages; diameters between2 and 6 microns for the tracheobronchial region; diameters between 0.5and 3 microns for alveolar administration. Reference should be made tothe following texts for further details:

International Commission on Radiological Protection (1994): Humanrespiratory Tract Model for Radiological Protection. Annals of the ICRPVol. 24, No. 1-3 Elservier Science Inc. Tarrytown N.Y.

Heyder J., Gebhart J., Rudolf G., Schiller C. F. and Stahlhofen W.(1986): Deposition of particles in the human respiratory tract in thesize range 0.005-15 μm Journal of Aerosol Science 17(5):811-825.

Stahlhofen W., Rudolf G., and James A. C. (1989): Intercomparison ofExperimental Regional Deposition Data. Journal of Aerosol Medicine 2(3):285-308.

From the aforegoing it is evident that to treat respiratory affectionsit is important that the dose of suitable medicament is administeredonly into the therapeutically appropriate region of the respiratorytract, to prevent wastage of medicament in addition to undesiredsystemic effects. To achieve this, a nebulizer vial must be used whichis able to generate an aerosol of the precise particle size distributioncharacteristics.

SUMMARY OF THE INVENTION

An object of the present invention is therefore to provide a nebulizervial for aerosol therapy which enables the MMAD to be varied.

It is also important that a nebulizer vial has a nebulization ratesuitable for the type of patient to be treated. In this respect,although it is true that increasing the nebulization rate acceleratesthe therapy, a high nebulization rate, although suitable for normaladult patients, can be excessive for determined patients such aschildren or seriously asthmatic patients, to the extent of makingcorrect administration of the medicament difficult.

Another object of the invention is therefore to provide a nebulizer vialof the aforestated type in which the nebulization rate can be varied.

As a nebulizer vial for aerosol therapy is often used for domiciliarytreatment by non-expert persons and can be used repeatedly for differentrespiratory pathologies, a further object of the invention is to providea vial of the aforesaid type in which the aerosol characteristics(particle size distribution and nebulization rate) can be varied on thebasis of the patient's therapeutic needs in a very simple manner withinthe ability of any patient.

The aforestated first object is attained by the nebulizer vial of thepresent invention, characterised in that, for diameter parity of thenozzle orifice, means are provided to vary the distance between thenozzle orifice and the flow breaker device. The flow breaker device maycomprise a flow breaker diaphragm. In this respect, it has been verifiedthat varying this distance varies the MMAD of the solution particles.

The means for varying said distance can comprise (for a predefinedorifice diameter of the nozzle) nozzles of different length, to mount onthe end of the compressed air tube (the flow breaker diaphragm beingfixed), so also varying in consequence the distance between the orificeof the compressed air tube (which is always in the same position) andthe orifice of the nozzle. Obviously, various series of nozzles can beprovided which differ in the orifice diameter of the nozzles.

As an alternative the same nozzle can again be used, but with a meanswhich, with one and the same nozzle fixed to the compressed air tube,enables either the elevation of the compressed air tube orifice to bevaried (and consequently the elevation of the nozzle orifice), or theposition of said flow breaker diaphragm to be varied relative to thecompressed air tube orifice maintained in a fixed position.

Preferably on that surface of the flow breaker diaphragm facing thenozzle orifice there is provided coaxial with the nozzle orifice a pegwhich, on replacing the nozzle with another of different length or byvertically moving the flow breaker diaphragm (if the nozzle is notreplaceable), approaches the nozzle orifice to a greater or lesserextent.

The aforestated second object is attained by providing a device foradjusting the flow of external air entering the vial as a result ofinhalation by the patient, this enabling the nebulization rate of thenebulizer vial to be adjusted.

To attain the aforesaid final object the nebulizer vial is formed in twoparts, of which a lower part contains the solution of medicament foraerosol therapy and comprises the compressed air feed tube and therelative nozzle, whereas the upper part comprises the flow breakerdiaphragm, the inlet enabling external air to enter the vial followinginhalation by the patient, and the aerosol exit conduit, the two partsbeing removably connected together.

The fact of forming the nebulizer vial in two parts as just describedcan be used to vary the distance between the nozzle orifice and the flowbreaker diaphragm, the two said parts of the vial then being formed andconnected together in such a manner as to be able to obtain differentdistances between the nozzle orifice and the flow breaker device.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will be more easily understood from the ensuingdescription of one embodiment thereof. In this description reference ismade to the accompanying drawing, in which the single FIGURE representsa very schematic vertical section through a nebulizer vial of theinvention, the section being taken on a plane passing through the axisof the compressed air feed tube.

DETAILED DESCRIPTION OF THE INVENTION

Observing the FIGURE it can be seen that the nebulizer vial 10 iscomposed of two parts, namely an upper part A and a lower part B. Toenable the vial 10 to be used, the parts A and B have to be connectedtogether (as shown in the FIGURE), this being achievable in variousways, for example by a screw connection, by a bayonet connection or by asnap clip connection.

As can be seen, the outer casing 12 of the part B is shaped as a cup,the base of which is sealedly traversed by a tube 14 for feedingcompressed air generated by a compressor (not shown) of the conventionaltype used for aerosol apparatus. The upper end of the tube 14 is taperedboth externally and internally (the internal taper causing the saidventuri effect), the tube 14 finally terminating with an exit orifice16.

A nozzle 18 is mounted concentrically on the upper end of the tube 14 sothat between the nozzle and the tube, there remains an interspace 20which lowerly communicates with a solution 22 of a determined medicamentwhich occupies, to a determined level, the lower part of the cup-shapedcasing 12, which hence acts as a reservoir for the medicament solution.To center the nozzle 18 about the tube 14, this latter or the nozzle 18can be provided with radial spacer ribs (not shown for simplicity). Inthe illustrated example, between the upper end of the compressed airtube 14 and the corresponding inner surface of the nozzle 18 thereexists a free space 21 which acts as a preatomization chamber.

Above the nozzle 18 and coaxial thereto there is disposed a conduit 24,the lower end of which is partly closed by a bar-shaped flow breakerdiaphragm 26, the two ends of which are connected to the conduit 24. Atthe upper end of the conduit 24 there is provided a regulator devicewhich comprises a flow regulator cock shown very schematically andindicated overall by 32. The flow regulator cock 32 enables thenebulization rate to be continuously adjusted from a minimum value to amaximum value, in order to adapt the aerosol leaving the vial to therespiration characteristics of the patient. In the FIGURE the arrows 38indicate the entry of external air resulting from the suction exerted bythe patient on the upper end of an aerosol exit channel with which thenebulizer vial 10 is provided. A usual mouthpiece, a respiratory mask ora nasal adapter (not shown) through which the patient can inhale theaerosol can be connected to this upper end.

In the illustration example the bar 26 carries a peg 28, coaxial to thenozzle 18, which extends downwards and approaches the orifice 30 of thenozzle 18.

As already stated, one way of varying the MMAD of the particles of theaerosol produced by the vial 10 is to provide interchangeable nozzles 18of different length such that the distance between the orifice 30 of thenozzle 18 and the diaphragm 26 varies in accordance with the length ofthe nozzle 18. In the illustrated example the presence of the peg 28enables not only said distance but also the aperture of the orifice 30to be varied, this enabling the best results to be obtained. Another wayof varying said distance is to make the compressed air tube 14insertable to a greater or lesser extent (for this purpose referencemarkings can be provided thereon) into the cup-shaped casing 12 of thelower part B, so that the orifice 30 of the nozzle 18 (which in thiscase is fixed to the tube 14) approaches the diaphragm 26 to a greateror lesser extent. Another simple way of adjusting said distance is toconstruct the casing of the vial 10 in such a manner that the two partsA and B can be inserted or screwed into each other to a greater orlesser extent in order to achieve this object. As a variant, a number ofspacing connection stubs having different heights can be providedbetween the two parts A and B. Again, the external air conduit 24 (tothe lower end of which the diaphragm 26 is fixed) can be made verticallymovable relative to the rest of the vial 10, within determined limits,to enable said distance to be varied.

According to one embodiment of the invention, a vertical section throughthe vial 10 taken on a plane passing through the axis of the exitorifice 16 has an outer profile which is at least approximatelyelliptical, the minor axis of the ellipse passing through or inproximity to the orifice 30 of the nozzle 18.

Although already apparent from the aforegoing, the operation of thenebulizer vial 10 will now be briefly described.

After pouring the prescribed quantity of medicament solution 22 into thecup casing 12 of the lower part B (having obviously separated the twoparts A and B) and reassembling the two parts A and B, the compressedair compressor (not shown) is operated so that the compressed airreaches the lower end of the tube 14. As already stated, the exit ofcompressed air from the orifice 16 of the tube 14 causes particles ofsolution to be drawn through the interspace 20, to form an ascendingstream of air and solution particles which leaves from the orifice 30 ofthe nozzle 18 and strikes the diaphragm 26, to cause atomization of thesolution particles. As a result of the sucking action exerted by thepatient through the upper end of the aerosol exit channel 34—causingexternal air to be drawn through the conduit 24 upperly provided with asuitably flow regulator cock—the aerosol stream, formed as a result ofthe impact of the solution particles against the diaphragm 26 and theirmixing with the air entering through the conduit 24 and the apertures36, is directed towards the exit channel 34, to finally reach thepatient who, as stated, exerts the sucking action through a mouthpiece,mask or nasal adapter.

From the aforegoing it is apparent that the particle sizecharacteristics of the aerosol can be varied very simply directly by thepatient. The patient simply separates the two parts A and B of the vial10, and can then position in the vial 10 that nozzle 18 of appropriatelength to obtain the required MMAD, or replace the existing nozzle 18with one suitable for the particular therapy to be carried out. It isalso apparent that if the other aforesaid solutions for varying thedistance between the orifice 30 of the nozzle 18 and the diaphragm 26are adopted, this distance can again be varied very simply.

What is claimed is:
 1. A nebulizer vial for aerosol therapy, comprising:a tube fed at a first end with compressed air, the tube beingconstricted at its second end prior to an exit orifice to obtain aventuri effect, the orifice of the tube emerging from the free surfaceof a solution of an aerosol therapy medicament; a nozzle beingconcentrically mounted on the second end of the tube such that betweenthe tube and nozzle, there remains an interspace communicating with thesolution; a flow breaker device being provided above an orifice of thenozzle; an aerosol exit channel for formed aerosol and a conduit forentry of external air as a result of suction exerted by a patient on theaerosol exit channel; wherein, for diameter parity of the orifice of thenozzle, means are provided for varying the distance between the nozzleorifice and the flow breaker device; said means for varying the distancebetween the orifice of the nozzle and the flow breaker device comprisinga series of interchangeable nozzles of different lengths.
 2. Thenebulizer vial for aerosol therapy as claimed in claim 1, wherein themeans for varying the distance between the orifice of the nozzle and theflow breaker device comprise means enabling the elevation of the flowbreaker device to be varied relative to the orifice of the nozzle, withsaid orifice of the nozzle being fixed.
 3. The nebulizer vial foraerosol therapy as claimed in claim 1, wherein the means for varying thedistance between the orifice of the nozzle and the flow breaker devicecomprise means enabling the elevation of the exit orifice of thecompressed air tube to which the nozzle is fixed to be varied, with theflow breaker device being fixed.
 4. The nebulizer vial for aerosoltherapy as claimed in claim 1, wherein the flow breaker device comprisesa diaphragm disposed above the orifice of the nozzle.
 5. The nebulizervial for aerosol therapy as claimed in claim 4, wherein the diaphragm isdisposed at one end of the conduit without however closing said end, theother end of the conduit being open towards the outside to enableexternal air to enter following suction exerted by the patient on theaerosol exit channel.
 6. The nebulizer vial for aerosol therapy asclaimed in claim 4, wherein a lower face of the diaphragm facing theorifice of the nozzle comprises a downwardly extending peg coaxial tothe orifice and partly closing the orifice.
 7. The nebulizer vial foraerosol therapy as claimed in claim 1, wherein a regulator device isprovided for the external air entering through the conduit.
 8. Thenebulizer vial for aerosol therapy as claimed in claim 7, wherein theregulator device comprises a flow regulator cock.
 9. The nebulizer vialfor aerosol therapy as claimed in claim 1, comprising two parts, whereina lower part contains the aerosol medicament solution and comprises thetube and the nozzle; wherein an upper part comprises the flow breakerdevice, the conduit, and the aerosol exit channel; and said two partsbeing removably connectable together.
 10. The nebulizer vial for aerosoltherapy as claimed in claim 9, wherein the means for varying thedistance between the orifice of the nozzle and the flow breaker devicecomprise means enabling the two parts to be connected together to obtaindifferent distances between the orifice and the flow breaker device. 11.The nebulizer vial for aerosol therapy as claimed in claim 10, whereinthe means which enables the two parts to be connected together to obtaindifferent distances between the orifice and the flow breaker devicecomprises a series of spacing connection stubs between the two parts;said stubs having different heights.
 12. The nebulizer vial for aerosoltherapy as claimed in claim 1, wherein a preatomization chamber isprovided between the second end of the tube and the corresponding innersurface of the nozzle.
 13. The nebulizer vial for aerosol therapy asclaimed in claim 1, wherein a vertical section through the vial taken ona plane passing through the axis of the orifice has an outer profilewhich is at least approximately elliptical, the minor axis of theellipse passing through or in proximity to the orifice of the nozzle.14. The nebulizer vial for aerosol therapy as claimed in claim 1,wherein on a given nozzle length, a series of nozzles having differentdiameters of the orifice is provided.